Method of performing an intramuscular injection

ABSTRACT

Hypodermic ampoules of the contained-needle type, a method of assembling and filling such ampoules, and combinations of such ampoules with so-called &#39;&#39;&#39;&#39;applicators&#39;&#39;&#39;&#39; for actuating the ampoules to make injections are disclosed. Each of several ampoule forms has at least one cylindrical, medicament-containing chamber and a plunger closing one end thereof. A hollow needle is fixed to the plunger and is initially contained within such a chamber. The other end of the ampoule is sealed by a diaphragm which is pressed against a beaded end portion of a cylinder and is sealed thereto by a cup-shaped clip which snaps over the beaded end portion to thereby compress the diaphragm against the end portion. The clip has a peripheral rim about a recessed bottom end which stretches the patient&#39;&#39;s skin to facilitate the injection. According to one aspect of the invention, such an ampoule is designed to perform a subcutaneous injection. According to a further aspect of the invention, such an ampoule is designed to perform an intramuscular injection. According to a still further aspect of the invention, the ampoule includes multiple chambers for premixing a medicament with at least one other medicament and injecting the mixture, either subcutaneously or intramuscularly. Applicators designed to receive and hold the several forms of ampoules and to actuate them as required by their particular forms and functions provide several applicatorampoule combinations of novel structure and functions.

United States Patent Hurschman METHOD OF PERFORMING AN INTRAMUSCULARINJECTION [56] References Cited UNITED STATES PATENTS 1.651349 11/1927Gaertner 128/218 R 2.704072 3/1955 Sarnoff 128/218 D PrimaryExaminer-Richard A. Gaudet Assistant Examiner-J. C. McGowan Attorney,Agent, or Firm-McNenny, Farrington, Pearne & Gordon [57] ABSTRACTHypodermic ampoules of the contained-needle type, a

1 Mar. 19, 1974 method of assembling and filling such ampoules, andcombinations of such ampoules with so-called applicators for actuatingthe ampoules to make injections are disclosed. Each of several ampouleforms has at least one cylindrical, medicamenbcontaining chamber and aplunger closing one end thereof. A hollow needle is fixed to the plungerand is initially contained within such a chamber. The other end of theampoule is sealed by a diaphragm which is pressed against a beaded endportion of a cylinder and is sealed thereto by a cup-shaped clip whichsnaps over the beaded end portion to thereby compress the diaphragmagainst the end portion. The clip has a peripheral rim about a recessedbottom end which stretches the patients skin to facilitate theinjection. According to one aspect of the invention, such an ampoule isdesigned to perform a subcutaneous injection. According to a furtheraspect of the invention, such an ampoule is designed to perform anintramuscular injection. According to a still further aspect of theinvention, the ampoule includes multiple chambers for premixing amedicament with at least one other medicament and injecting the mixture,either subcutaneously or intramuscularly. Applicators designed toreceive and hold the several forms of ampoules and to actuate them asrequired by their particular forms and functions provide severalapplicator-ampoule combinations of novel structure and functions.

1 Claim, 22 Drawing Figures PATENTEHHAR 19 I974 SHEET 5 0F 5 {fry/4wlllllllllllllil METHOD OF PERFORMING AN INTRAMUSCULAR INJECTJON Thisapplication is a division of application Ser. No. ll4,493, filed Feb.ll, 1971, now U.S. Pat. No. 3,735,761, issued May 29, 1973.

BACKGROUND OF THE INVENTION This invention relates to disposablehypodermic ampoules that provide a chamber containing both a medicamentto be injected and the hypodermic needle through which the injection ismade, the injection being performed by collapsing or otherwise actuatingthe device to project the pointed end of the needle through apuncturable wall of the ampoule and then into the patient while reducingthe volume of the medicamentcontaining chamber to express the medicamentthrough the needle and into the patient. Such ampoules are referred toherein by the generic designation, contained-needle type. V

Ampoules of this general character are represented, for example, bytwoseries of United States patents granted, respectively, to Russell P.Dunmire and to Stanley J. Sarnoff or Stanley J. Sarnoff et a]. Theprincipal ones of those patents to Dunmire are U.S. Pat. Nos. 2,769,443,3,094,987, 3,094,988, and 3,236,237, and the principal ones of thosepatents to Sarnoff (or Sarnoff et al.) are U.S. Pat. Nos. 2,704,072,2,832,339, 3,302,955, and 3,396,726. The devices of. those patents ofDunmire and Sarnoff (or Sarnoff et al.) involve a particularlyadvantageous mode of operation in that the medicament is injected intothe patient from the pointed end of the needle as ittrave lslongitudinally to its maximum depth of penetration, thus distributingthe medicament for faster absorption and minimizing discomfort andtrauma sometimes occasioned by injecting all of the medicament in onelocation after the needle has been inserted to the maximum depth. Theyalso greatly reduce the chances for contamination of the medicament orthe needle; they require little or no skill on the part of the user, andeven make self-injection safe and practical; and they have numerousother inherent advantages which the art has long recognized. However,none of, the devices of that general type has yet been perfectedsufficiently for widespread use.

For inspection purposes after filling, it is important that ampoules ofthe contained-needle types disclosed in the Dunmire and Sarnoff (orSarnoff et al.) patents have transparent walls. in order to make thecollapsible walls of the ampoules of the Dunmire patents transparent, ithas been necessary to mold them from synthetic resin materials which,because of their possible reactivity with certain medicaments duringprolonged periods of storage after filling and before use, have limitedthe use of such ampoules. Although the components of such devices couldbe molded of suitably inert natural rubber, that material does not havethe transparency required for inspection after filling and, therefore,cannot be used for many applications.

Although the ampoule shell walls that are in contact with a containedmedicament during storage of the devices of the Sarnoff (or Sarnoff etal.) patents could be made of transparent, inert, glass tubing andsufficiently inert, molded rubber, end closures for the tubing, so as toavoid the aforementioned inspection problem, the forms of devices shownin those patents have involved various structural, assembly,operational, and/or cost problems that have limited their usefulnessand, hence, their commercial acceptance. For example, the puncturableend wall of the devices of those patents of Sarnoff (or Sarnoff et al.)are incapable of sealing against the skin of a patient as required toavoid loss of medicament by seepage between the ampoule end wall andsurface of the skin, particularly in the case of such devices designedand used for making relatively shallow subcutaneous injections. Whendesigned as shown in those patents and used as intended for makingintramuscular injections, the flow of medicament out of the pointed endof the needle begins as soon as the needle point emerges from theampoule for penetrating the skin, and such flow continues until theneedle has penetrated to its maximm depth in the muscle layer. Theresult is neither a normal subcutaneous injection nor a normalintramuscular injection but, rather, is a combination of the two thathas been acceptable only for very limited injection purposes. Thedevices of those Dunmire patents,-on the other hand, were ideal formaking subcutaneous injections, but for the same reason as the devicesof the patents of Sarnoff (or Sarnoff et al.), were incapable of givinga normal intramuscular injection. a

Devices have been proposed which are designed for making subcutaneousinjections. One such device is shown in U.S. Pat. No. 3,396,726 toSarnoff and includes a cylinder which defines a medicamentcontainingampoule. A piston driven needle is contained in the ampoule and one endof the ampoule is closed by a pierceable diagphragm. The cylinder isonly partially filled by the medicament so that the needle may be driventhrough the diaphragm and into the muscle prior to ejection ofthemedicament from the needle. However the disclosed method ofperforming the intramuscular injection according to the Sarnoff patentnecessitates the injection of air into the patient. When an injection isperformed by skilled personnel, there is little danger if air isinjected into the patient. Desirably, however, an injection deviceshould be designed so that an injection may be performed by unskilledpersonnel such as the patient himself. Uns'killed personnel may injectair into a blood vessel and it is therefore important to provide anampoule and an injection procedure which eliminates this possibility.

As further examples of problems not heretofore solved, some of thedevices of those patents of Sarnoff (or Sarnoff et al.) and of otherprior art, in order to ensure a proper seal between a tubular, glasssidewall of an ampoule and a puncturable diaphragm closing one endthereof, have included diaphragm retaining members that are integralparts of an applicator for actuating the ampoule (e.g., U.S. Pat. No.2,832,339 to Sarnoff et al.), or have included diaphragm retainingmembers that hold the medicament-containing ampoule in operativeposition within an applicator (e.g., U.S. Pat. No. 2,866,458 to Rain,Jr.) Such structures necessitate assembly and filling of an ampouleduring the assembly of the ampoule within an applicator. However, it isfrequently desirable to assemble and fill an ampoule of thecontained-needle type and then ship that ampoule to the user so that theuser may install it in an applicator.

A more acceptable solution to the problem of sealing a diaphragm to amedicament-containing cylinder may be found in U.S. Pat. No. 2,704,073to Jensen. In the Jensen patent, the diaphragm is sealed against one endof a cylinder by a cup-shaped clip which snaps over a beaded end portionof the cylinder to press the diaphragm against the end of the cylinder.This permits an ampoule to be assembled prior to shipment and laterinstalled in an ampoule applicator. However, it provides a relativelylarge, substantially flat, skincontacting surface that is incapable ofsealing against loss of medicament by seepage between that end wall andthe skin.

Moreover, neither the aforementioned Jensen patent nor any of thepreviously mentioned patents of Sarnoff et al. and Hein, Jr. provides apuncturable diaphragm that will permit an ampoule that is substantiallyfull of liquid to be actuated to reduce the liquid chamber volume andforce the needle through the diaphragm without occassionally (at least)creating a hydraulic lock that either bursts'the ampoule or preventsinitial movement of a plunger for causing the needle to puncture thediaphragm and thereby release the liquid for injection. Dunmire U.S.Pat. Nos. 3,094,988 and 3,236,237, which disclose solutions of thelatter problem in the case of molded plastic ampoules, fail to providesolutions for the other problems described above.

The applicator disclosed in U.S. Pat. No. 3,236,237 to Dunmire involvesa special endwall construction that cooperates with the specialdiaphragm of Dunmire U.S. Pat. No. 3,094,988 to perform the desirablefunctions set forth therein. However, in many instances it is desirableor necessary to perform an injection without employing an applicator.Furthermore, it may be desirable to perform an injection with anapplicator different than the particular kind set forth in that patent,so that the advantages afforded by the teachings of the patent must belost or achieved in some other manner.

A number of drug compounds, including some antibiotics, some vaccines,and several other injectable products, require that an active ingredient(usually in a' powder form) be mixed with an injection vehicle (usuallywater) shortly before administration. One widely accepted procedure formixing powder and liquid medicament components is to provide them inseparate vials, each having its own rubber stopper closing its outletopening. The liquid is withdrawn from its vial by a needle and syringeand is then injected into the vial containing the powder. The thus mixedliquid and powder in the latter vial, after shaking it where required,are withdrawn as a dispersion by the same needle and syringe, and theinjection is effected therewith in a conventional manner.

Attempts have been made to provide a multicompartment vial whereinliquid and solid components to be mixed prior to injection areseparately contained in a manner that permitsmixing them within thecommon via]. For example, U.S. Pat. No. 2,495,942 to W. A. Nosekprovides an outer container having an inner container mounted therein.The outer container contains a liquid medicament and the inner containercontains a solid medicament. The inner container is releasably sealed toa stopper which closes both containers. By depressing the stopper, theinner container is released so that its solid contents may mix with theliquid. The mixture is then withdrawn by piercing the stopper with theneedle or a hypodermic syringe. Such an arrangement, however, is notreadily applicable to the containedneedle type of hypodermic ampoules towhich the present invention relates, apart from other objectionsthereto.

Another proposal for providing a multichamber container is set forth inU.S. Pat. No. 3,342,180 to Sandhage et al., dated Sept. 19, 1967. Inthat patent, the patentees provide a vial which is separated into twochambers by a plunger. Powder is provided in a lower chamber and liquidis provided in the upper chamber. The plunger is provided with a one-waycheck valve so that, upon retraction of the plunger, the liquid isforced through the valve and into the compartment containing the powder.The vial is provided with an external needle at its lower end so thatthe mixed medicament may be injected into the patient. Again, apart fromother objections thereto, such an arrangement is not readily applicableto the contained-needle type of hypodermic ampoules to which the presentinvention relates.

As a result of the foregoing problems, and numerous others, priorhypodermic ampoules of the containedneedle type, to which the presentinvention relates, have all been subject to severe limitations on theirpractical utility, and their uses have been restricted accordingly. Thepresent invention is directed to the provision of a basic ampoule designof the containedneedle type that is adaptable for making bothsubcutaneous and intramuscular injections, either of a containedpremixed medicament or of two or more separated medicament componentsthat are mixed in the ampoule itself. A major objective is to achieveall of this 1. with a maximum utilization of basic parts of both theampoules and applicators therefor,

2. with a minimum variation in the techniques of assembling, filling,and using the ampoules, and

3. while overcoming or avoiding the many problems that have heretoforeprevented general use of the desirable, contained-needle type ofinjection device.

SUMMARY OF THE INVENTION In its simplest form, this invention provides adisposable ampoule of the contained-needle type having a rigid,cylindrical sidewall, an actuating, needle-carrying plunger in one endthereof, and an improved, skinengaging, puncturable, endwall assembly atits opposite end that is suitable for use, also, in the other forms ofthe invention disclosed herein and for use with a variety of applicatorsor without employing any applicator. The improved, puncturable, endwallassembly includes the main features of the puncturable diaphragm ofDunmire U.S. Pat. No. 3,094,988 and a novel clip for fastening thediaphragm to the cylindrical sidewall.

The clip according to this invention is cup-shaped and has a cylindricalsidewall provided with an annular groove which snaps over a radiallyextending, circumferential bead adjacent the end of the cylinder. Thebottom of the clip has a central opening therein or receiving a central,needle-guiding, gland portion of the puncturable diaphragm. The externalbottom surface of the clip is concave and tapers inwardly from an outerrim portion to the central opening so that, upon engagement of the clipwith the skin to effect an injection, the skin is stretched to resistindentation by the gland and produce a more reliable seal between thegland and the skin, while urging the gland axially inwardly toward thepoint of the needle to facilitate actuation of the ampoule. This latterfeature permits the, ampoule to be,

employed with or without an applicator. If an applicator is to beemployed, however, it need not be specially designed to itself performthe skin-stretching function as disclosed in Dunmire US. Pat. No.3,236,237.

This invention also provides an intramuscular, disposable, hypodermicampoule which includes a longer cylindrical sidewall closed at one endby the puncturable diaphragm assembly and closed at its other end by aslidable plunger carrying a needle with a longer cannula. In this case,the cylinder is only partially filled with medicament. Prior to aninjection, the plunger is partially depressed by pushing it toward thediaphragm so that the needle projects through and beyond the dia phragmand so that air within the ampoule is expelled prior to initiating theinjection. The projecting end of the needle is then pushed through theskin and fascia layers and into the muscle of the patient, and theplunger is completely depressed to inject the medicament as the needletravels further into the muscle. A removable protective shield for thepartially advanced needle is preferably provided as an attachment to thepuncturable clip and diaphragm assembly and is removed just prior tomaking the actual injection. Otherwise, this form of the inventiondiffers from the first described form primarily in the lengths of thecylindrical sidewall and needle cannula.

This invention also provides a multichamber, hypodermic device whichincludes first and second coaxially disposed cylinders. The cylindersrespectively provide first and second, medicament-containing chambers,the adjacent ends of which are separated by a first, puncturable,piston-like diaphragm. This first diaphragm extends across and aroundthe end of the first cylinder to close and seal the same and is slidablymounted in the adjacent end of the second cylinder to close and sepa'rately seal the sameflhese two seals are exposed to and separated by theambient atmosphere so as to avoid liquid seepage from one chamber intothe other. The other end of the first cylinder slidably carries aplunger.

A hypodermic needle is mounted on the plunger with its pointed endextending axially toward a pierceable, central portion of the firstdiaphragm. The other end of the second cylinder is closed and sealed bythe above describedppuncturable, clip and diaphragm assembly having itspierceable portion also axially aligned with the. pointed end of theneedle.

The first chamber is partially filled with a first medicament, usuallyin powder form, and the excess space therein is preferably partiallyevacuated. The second chamber is filled with a second, liquid medicamentor vehicle for the first medicament. These medicament components aremixed by partially depressing the plunger so that the pointed end of theneedle cannula pierces the first diaphragm. The partial vacuum in theexcess space in the first chamber facilitates the flow of liquid fromthe second chamber through the needle and into the first chamber asthetirst diaphragm moves toward and into engagement with the seconddiaphragm, thus mixing the two medicaments. When the second chamber isexhausted and its volume reduced essentially to zero in this manner, aninjection may be effected by pressing the puncturable clip and diaphragmassembly against the skin of a patient and further depressing theplunger to the end of its stroke.

This invention also provides similar multichamber deviceslike theonelast described but with the similar provision in the second cylinder ofone or more additional, coaxially disposed chambers containingadditional, liquid medicament components to be sequentially mixed in alike manner with the first two components prior to making the actualinjection.

A basic applicator design is provided for receiving and actuating eachof the several ampoule forms to perform the particular injections forwhich each is designed.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of asingle chamber ampoule according to this invention.

FIG. 2 is an enlarged, cross-sectional view, the plane of the sectionbeing indicated by the line 2--2 in FIG. 1.

FIGS. 3 and 4 are cross-sectional views similar according to FIG. 2, butshowing the ampoule in an applicator and showing component parts of theampoule and applicator in positions attained during an injection.

FIG. 5 is a cross-sectional view of an ampoule which is adapted toperform an intramuscular injection according to a further aspect of thisinvention.

FIG. 6 is a cross-sectional view similar to FIG. 5, but showingcomponent parts of the ampoule in position attained prior to aninjection.

FIG. 7 is a cross-sectional view similar to FIG. 6, but showing theampoule mounted in an applicator and ready for an injection.

FIG. 8 is a cross-sectional view similar to FIG. 7, but

showing the ampoule in a position performing an injection.

FIG. 9 is a perspective view of a multichamber hypodermic ampouleaccording to a further aspect of this invention.

FIG. 10 is a cross-sectional view of the ampoule of FIG. 9, the plane ofthe section being indicated by the line 10l0 in FIG. 9.

FIGS. 11, 12, and 13 are cross-sectional views similar to FIG. 10, butshowing component parts of the ampoule in positions attained afterinitiating 'a mixing operation, completion of the mixing operation, andcompletion of an injection operation, respectively.

FIG. 14 is a cross-sectional view of a multichamber hypodermicampouleaccording to a further aspect of this invention. 1 i

FIG. 15 is a cross-sectional view of a multichamber hypodermic ampouleaccording to a still further aspect of this invention. the cm.

FIGS. 16 and 17 are cross-sectional views illustrating the componentparts of the ampoule of FIG. 15 in posi tions attained at the completionof a mixing operation and after further actuation to ready it for makingan injection, respectively.

FIG. 18 is a perspective view of a needle which may be employed incombination with devices according to this invention.

FIGS. 19 and 20 illustrate progressive filling and assembly operationsto produce the ampoule illustrated in FIGS. 9 through 13. i

FIG. 21 is a fragmentary perspective view of an ampoule retaining clipprovided in the applicators illustrated in FIGS. 7, 8, and 17.

FIG. 22 is a bottom end view of an ampoule mounted in the applicatorillustrated in FIGS. 7, 8, and 17.

DETAILED DESCRIPTION OF THE INVENTION Referring now to the drawings, andparticularly to FIGS. 1 through 4, a single chamber ampoule 10 isillustrated. The ampoule 10 is adapted toperform asubcutaneous injectionand includes a cylinder 11. The cylinder 11 is preferably made fromglass tubing and has a radially extending annular bead 12 at one end.

. That end of the cylinder 1 I is closed by a diaphragm 13 which ispressed against it by a plastic clip 14. The clip 14 is a cup-shaped andhas an inner annular groove 15 in its cylindrical sidewall which snapsover the bead 12. The clip 14 also includes a bottom wall 14a having acentral aperture 14!) therethrough. The bottom wall 14a has a concaveoutside surface which includes an outer rim 14c and which tapersupwardly toward the aperture 14!).

The diaphragm 13 is preferably molded from rubber and is shaped tofunction in accordance with the teachings of US. Pat. No. 3,094,988 toDunmire. It includes an outer, annular portion 16, a thick, elongated,centrally located, needle guiding and liquid sealing gland l7, and arelatively thin, flexible, corrugated, intermediate portion 18connecting the gland and the outer portion to permit relative axialmovement therebetween. The gland extends through the aperture 14b in theclip 14. An axial needle passage 19 may extend into the upper end of thegland from the inside and terminates short of the opposite, lower end ofthe gland to form a thin, easily puncturable wall 20 closing the bottomof the passage. Alternatively, this needle passage may be omitted whenmolding the diaphragm and, in effect, be formed by partial piercing ofthe gland by the needle during assembly of the ampoule.

The other end of the cylinder 11 is closed by a plunger 21 which is alsopreferably molded from rubber and formed to have a sliding interferencefit with the inner sidewall of the cylinder 11. The plunger 21,diaphragm 13, and cylinder 11, together, define a chamber 22 which issubstantially filled with a liquid medicament.

Entirely enclosed within the chamber 22 is a hypodermic needle 23 (FIG.18) which is preferably of the type disclosed in U.S. Pat. No. 3,l73,200to Dunmire et al. The illustrated circular base 24 at the butt end ofthe needle 23 is mounted on the plunger 21 so that the needle is insubstantial axial alignment with the cylinder 11 and has a pointed end25 projecting downwardly and received within the axial needle passage 19of the diaphragm gland 17 in position to be forced through the thin wall20 of the gland. Mounting of the needle base 24 on the plunger 21 iseffected by snapping the peripheral edge of the needle base under anannular lip 26 that is an integral part of the plunger. Flow into thebutt end of the needle from the chamber 22 occurs through an opening 27in the cannula wall adjacent the base 24 of the needle.

An injection is effected by first pressing the diaphragm gland 17 firmlyagainst the patients skin S, thus indenting the skin until the rim 14cof the bottom of the clip 14 also firmly engages the patients skin. Asmay be seen in FIGS. 3 and 4, when the clip 14 and the gland 17,together, firmly engage the skin S, the skin is stretched and domesupwardly to thereby seal it more tightly against the gland while forcingthe gland axially inwardly toward the pointed end 25 of the needle 23.Force is then applied to the upper end of the plunger 21 (eithermanually or by means of an ampoule applicator) to move it downwardlytoward the diaphragm 13 so that the needle 23 penetrates the gland wall20 (see FIG. 3) and enters the patients skin. As the plunger isdepressed in this manner, the liquid medicament in the chamber 22 isforced through the opening 27 in the upper end of the needle, throughthe needle cannula, and into the subcutaneous tissue of the patient. Byreason of the simultaneous upward pressure of the skin S on the gland 17and the outward flexibility of the corrugated diaphragm portion 18, theneedle is easily driven through the gland wall 20 before hydraulicpressure within the ampoule can block movement of the plunger. Also, theseal between the gland 17 and the skin S virtually prevents any seepageof medicament therebetween as the point of the needle moves into theskin layer and thereafter. Because both of these advantages areobtainable with the present invention with or without the use of anapplicator, since both result from the new construction of the ampoule,itself.

If force is applied to the upper end of the plunger 21 by means of anapplicator, the applicator may be of the type shown and described in thecopending application of Hurschman, Ser. No. 114,423, filed Feb. 11,197]. A lower end portion 28 of that applicator is illustrated in FIGS.3 and 4. The ampoule 10 is mounted within the portion 28 by abayonet-type connection between the ampoule 10 and the portion 28. As ismore fully set forth in the application of I-Iurschman, this connectionis effected by providing axially extending, diametrically opposed slots(not shown herein) through an inwardly extending flange portion 29 ofthe applicator and by providing cooperating, radially extending lugs 14don the clip 14. The lugs 14d are received within the slots and enterchannels 29a and 29b which extend in a clockwise direction and taperradially inwardly toward the inner cylindrical sidewall of the portion28. The

ampoule may be removably retained in the applicator by inserting thelugs 14d into the slots and turning the clip 14 in a clockwise directionuntil the lugs 14 d firctionally engage the inwardly tapering sidewallsof the channels 290 and 29b. The means to apply force to the plunger 21includes a spring biased force applying head 280 which is held in aretracted position illustrated in FIG. 3 by detent means (not shown).When the detent means is released, the force applying head drives theplunger 21 to the position illustrated in FIG. 4.

Referring now to FIGS. 5 through 8, a single chamber ampoule 30 isillustrated. The ampoule 30 is adapted to perform an intramuscularinjection and includes a cylinder 31 which is preferably made from glasstubing. One end of the cylinder 31 is provided with a radially extendingannular bead 32, and that end of the cylinder is closed by a rubberdiaphragm 33 that may be identical with the diaphragm 13 of FIGS. 2-4.The diaphragm 33 is pressed and held against the head 32 by a clip 34similar to the clip 14 of FIGS. 2-4. The other end of the cylinder 31 isclosed by a rubber plunger 41 having an enlarged portion 42 which formsa sliding interference fit with the inner sidewall of the cylinder 31.The plunger 41 is provided with an axially extending reduced upperportion 43 which initially extends beyond the cylinder 31.

The plunger 41, diaphragm 33, and cylinder 31, together, define achamber 44 which is partially filled with a liquid medicament. A spaceSp (FIG. 5) is provided between the level of the medicament and theinitial position of the plunger, and the axial extend of the portion 43of the plunger 41 corresponds to the axial extent of the space Sp.

Contained within the chamber 44 is a needle 45 which may be identicalwith theneedle 23 illustrated in FIGS. 2-4 and 18 except for having alonger cannula and is disposed and mounted in the chamber similarly tothe arrangement of FIGS. 2-4. A needle guard 46 is .removably fixed tothe clip 34 and extends axially therefrom. The needle guard 46 ispreferably of transparent plastic, is cup-shaped, and hasan open mouthwhich forms an interference fit with an annular, axially projectingshoulder portion 47 of the clip 34. For purposes which will hereinafterbecome apparent, the guard 46 so provided with a knurled bottom rib 48and has an axial extent which is greater than the space Sp.

To ensure an intramusculartype injection, the needle 45 must passthrough .the skin, underlying surface layers of fat, and the fascialayer and enter the muscle prior to medicament flow through the needle.Therefore, the chamber 44 is designed so that its volume is greater thanthe volume of medicament contained therein. Prior to effecting aninjection, the plunger 41 is depressed until the upper end of theportion 43 is level with the top of the cylinder 31, at which point thelower end of the plungercontacts the surface of the liquid in thechamber 44. During this depression operation, the needle 45 pierces thediaphragm 33 and the air or gas in the space Sp is substantiallyexpelled through the needle. This operation is most convenientlyperformed by placing the needle guard 46 on a flat surface and pressingthe plunger portion 43 downwardly until the ampoule 30 achieves thecondition illustrated in FIG. 6. If desired, the plunger may bedepressed in this manner until the appearance of a drop of medicament atthe point of the needle (visible through the transparent sidewall of theneedle guard 46) indicates the elimination of substantially all air orgas from the chamber 44. This operation projects the needle 45 apredetermined distance beyond the diaphragm 33, which distancesubstantially corresponds to the normal maximum depth of the musclebeneath the skin of the patient, and air or gas in the chamber 44 issubstantially fully expelled in the process.

After achieving the condition illustrated in FIG. 6, an intramuscularinjection may be effected by manually removing the needle guard 46,inserting the needle through the skin, fatty layer, and fascia layer andinto the muscle, and then completely depressing the plunger 41. Apreferred method of effecting an injection, however, is to employ anapplicator. As fragmentarily shown herein, such an applicator includes aspringbiased plunger 50 (FIGS. 7 and 8) mounted within a casing 51. Anapplicator adapted to perform an intramuscular injection includes anelongated, metal, bellshaped mouth portion 52 which is provided with diametrically opposed inner spring clips 53 or the like (see FIG. 21) whichare spot welded to the inner sidewall of the portion 52. The clips 53retain the ampoule diaphragm clip 34in the position illustrated in FIG.7, so that the partially advanced needle 45 is initially recessed in theapplicator. With the needle guard attached, the ampoule 30 is mountedwithin hte applicator by inserting a pair of diametrically opposed lugs3411 provided on the clip 34 into a cooperating pair of slots -52a (FIG.22 which extend axially through a radially inwardly extending flange52b. This operation is performed by grasping the knurled bottom rib 48on the needle guard 46. The ampoule is pushed upwardly into the casing51 until thelugs 34a are above the level of .the spring clips and isthen rotated until the lugs 34a rest on the clips 53 (see FIG. 7). It isdesirable to remove the guard 46 after the ampoule 30 is mounted in theapplicator to prevent contamination of the needle. The needle guard isremoved by pulling one portion of the rib 48 downwardly while pushing adiametrically opposed portion of the rib upwardly since an axial forceapplied to the rib may disengage the lugs from their retaining springclips. After the needle guard is removed, the mouth 52 of the applicatoris placed against the skin of the patient and the plunger is fired. Theapplicator spring clips 53 are designed so that they release the ampoulediaphragm clip 34 prior to movement of the plunger 41 relative to theampoule clyinder 31. To this end, the springs are designed so that theforce required to drive the lugs 34a from their retained position isless than the force required to move the plunger 42 relative to thecylinder 31. In this manner, the needle 45 is driven into the muscle M(FIG. 8) prior to injection of the medicament. After the needle 45enters the muscle, the plunger 41 again moves toward the diaphragm 33 toperform the injection by expressing the medicament through the needle 45as it is driven further into the muscle M. The injection is completewhen the plunger engages the diaphragm.

Referring now to FIGS. 9 through 13 of the drawings, a multichamberampoule is illustrated. The ampoule 110 is adapted to perform asubcutaneous injection and includes a first cylinder 111 and a secondcylinder 112 of larger diameter, both being preferably made from glasstubing. One end of the first cylinder 11 1 has a radially extendingannular head 1 13 which is received within an annular groove 114provided in a first diaphragm 115. The first diaphragm 115 is preferablymade from rubber and is received with an interference fit within one endof the second cylinder 1 12. This radially compresses this diaphragm andcauses it to inore tightly embrace the cylinder bead 113.

The other end of the first cylinder 111 is closed by a rubber plunger 116 which, together with the first cylinder 111 and the first diaphragm115, defines a first chamber 117. The plunger 116 is preferably made ofrubber and has an interference fit in the first cylinder.

Entirely enclosed within the first chamber 117 is a hypodermic needle118 which may be identical with the needle 23 illustrated in FIGS. 2-4and 18 except for having a longer cannula. The illustrated circular base119 at the butt end of the needle 1 18 is mounted on the plunger 116similarly to the arrangement of FIGS. 2-4 so that the needle is insubstantial axial alignment with the cylinder 111 and has a pointed end120 projecting downwardly and into the diaphragm 115 in position to.

be forced through the unpiercedl remainder thereof.

As will be hereinafter explained in greater detail, the chamber 1 17 isat least partially filled with a powdered medicament 123 and ispartially evacuated. A sliding interference fit between the diaphragm115 and the inner sidewall of the cylinder 112 aids in sealing the bead113 within the annular groove 114. Friction between the plunger 116 andwall of the cylinder 111 and resistance of the diaphragm 115 topenetration by the needle 118, of course, prevent the plunger 116 fromprematurely moving toward the diaphragm 115.

The other end of the second cylinder 112 is closed by a second diaphragm124 and a clip 125 constructed and operating like the previouslydescribed similar diaphragm and clip of FIGS. 2-4, the diaphragmcomprising portions 127, 128, and 129 corresponding to portions 16,17,and 18 of the diaphragm of FIGS. 24 and having a similar needlereceiving passage 130 ending in a puncturable wall 131 closing thebottom of the passage.

The first diaphragm 1 15, second diaphragm 124, and cylinder 112,together, define a second chamber 132. The second chamber 132 is filledwith a liquid medicament in a manner which will hereinafter beexplained.

The liquid medicament in the second chamber is mixed with the solidpowder medicament in the first chamber prior to injection in a mannerwhich will now be explained. The plunger 116 is pushed axially towardthe first diaphragm 115 until the needle 118 pierces this diaphragm andprovides communication through the needle between the second chamber 132and the first chamber 117, as shown in FIG. 11. Once communication isestablished between these chambers, the liquid is drawn upwardly intothe first chamber by downward movement of the cylinder 111 and firstdiaphragm 115, together, into engagemnt with the second diaphragm 124,as shown in FIG. 12. At this stage, the pointed end of the needle 118,which previously pierced the first diaphragm 115, has entered the gland128 of the diaphragm 124.

To ensure that the pointed end of the needle will not be initiallyextended too far beyond the first diaphragm 115 after it pierces thatdiaphragm, the plunger 116 is provided with a centrally raised portionwhich extends beyond the end of the cylinder 111 when the ampoule isinitially assembled. The raised portion 140, therefore, extends beyondthe end of the cylinder 111 for a distance which'substantiallycorresponds to the thickness of the portion of the diaphragm 115 to bepierced plus the desired extension of the needle beyond the diaphragm115 during the mixing operation. To perform the penetration operation,therefore, the raised portion 140 is depressed until its upper or outerend is flush with the top mouth of the cylinder 111, as illustrated inFIGS. 11 and 12.

When the ampoule 110 is in the condition illustrated in FIG. 12 and theampoule has been inverted several times or vigorously shaken as reliablemixing of the medicament components may require (generally notnecessary), the ampoule is in a condition suitable for making asubcutaneous injection. To perform the injection, the diaphragm 124 isplaced adjacent the patients skin and the plunger is fully depresseduntil it assumes the 4 position illustrated in FIG. 13. During theplunger depressing step, the needle penetrates the wall 131, and fluidis exhausted from the first chamber through the needle opening adjacentthe plunger 116 and through the opening in the end of the needle as theneedle penetrates the skin and subcutaneous fat of the patient.

Referring now to FIG. 14, an ampoule is illustrated. The ampoule 150 issuited for performing an injection requiring the premixing of two ormore liquid medicaments with each other or with each other and with asolid medicament. The ampoule 150 includes a first cylinder 151 which ispreferably made from'glass and which has a beaded rim portion 152 at itslower end. The rim portion 152 is received within an annular groove 153which is provided in a first diaphragm 154. The diaphragm 154 closes oneend of the cylnder 151,

and the other end of the cylinder 151 is closed by a plunger 155. Aneedle 156 similar to the needles 23 and 118 (except for cannula length)is mounted on the plunger similarly to the arrangement of FIGS. 24. 5 Apointed end 159 of the needle 156 is received within a passage 160 inthe first diaphragm 154. The plunger 155, cylinder 151, and thediaphragm 154, together, define a first chamber 161. As will behereinafter explained in greater detail, the chamber 161 is partiallyevacuated during the assembly operation and is at least partially filledwith a liquid or powdered medicament 162.

The first diaphragm 154 is slidably received within a second cylinder163. The second cylinder 163 has its upper end closed by the firstdiaphragm 154 and has its lower end closed by a second diaphragm 164 anda clip 165 constructed and operating like the previously describedsimilar diaphragm and clip of FIGS. 24.

Intermediate diaphragms 167 and 168 are provided in the cylinder 163.The intermediate diaphragms 167 and 168, the diaphragms 154 and 164, andthe cylinder 163, together, define second, third, and fourth chambers169, 170, and 171, respectively. The chambers 169, 170, and 171 arefilled with different liquid medicaments. Y

The medicaments contained in the chambers 169-171 are mixed together,and that mixture is in turn mixed with the powder 162 in the followingmanner. The plunger 155 is pushed downwardly until the needle 156pierces the first diaphragm 154 to provide fluid communication betweenthe chamber 169 and the chamber 161. The fluid in the chamber 169 isdrawn through the hollow needle 156 and into the chamber 161. After theliquid in the chamber 169 is exhausted in this manner, the diaphragm 154contacts the diaphragm 167 and the pointed end 159 of the needle entersa passage 172 in the diaphragm 167. Further pressure on the plunger 155causes the needle 156 to pierce the diaphragm 167 to thereby draw liquidfrom the the chamber into the chamber 161 and move the diaphragm 167against the diaphragm 168. The pointed end 159 of the needle 156 thenenters a passage 173 in the diaphragm 168 and further pressure on theplunger 155 drives the needle 156 through the diaphragm 168 to therebydraw liquid from the chamber 171. After the liquid in the chamber 171 isexhausted, the diaphragm 168 contacts the diaphragm 164 and the pointedend of the needle is received within a passage 174 provided in thediaphragm 164.

After the several liquids are mixed with each other and with thematerial 162 in the chamber 161, the ampoule 150 is in a condition toperform an injection. This injection is performed by placing thediaphragm 164 against the skin of the patient and by depressing theplunger 155 until the plunger 155 contacts the diaphragm 154. It shouldbe appreciated that any number of liquids may be mixed in this mannerwith or without a powdered medicament, after which the ampoule, with orwithout an applicator of the kind partially shown in FIGS. 3 and 4, maybe used to make a subcutaneous injection in the general mannerpreviously described.

Referring now to FIGS. 15, 16, and 17, an ampoule is illustrated, Theampoule 180 may be employed to mix liquid and powdered medicaments priorto an injection, and may be employed to effect an intramuscular ratherthan subcutaneous injection. The ampoule 180 is generally similar to theampoule 110 in that it in cludes a first cylinder 181 which is closed atone end by a rubber plunger 182 and is closed at the other end by afirst diaphragm 183. A needle 184 is fixed to the plunger 182 in thesame manner previously described, and the diaphragm 183 is slidablyreceived in a second cylinder 185. The second cylinder 185 is closed atits lower end by a second diaphragm 186 and a clip 187 constructed andoperating like the previously described similar diaphragm and clip ofFIGS. 2-4. A needle guard 188 similar to the needle guard 46 of FIGS. 5and 6 is removablyfixed to the clip 187 and extends axially therefrom aspreviously described with reference to the latter figures of thedrawings.

The first cylinder 181, diaphragm 183, and plunger 182, together, form afirst chamber 190 which is evacuated and partially filled with apowdered medicament 191. The second cylinder 185 and diaphragms 183 and186, together, form a second chamber 192 which is filled with a liquidmedicament 193.

The medicaments 191 and 193 are mixed in a manner similar to the mixingprocedure set forth with regard to the ampoule 10 of FIGS. 9-13. Theplunger 182 is pushed axially until the needle 184 pierces the diaphragm183 and provides liquid communication be tween the chambers 190 and 192.When such commu nication is established, the diaphragm 183 moves intoengagement with the diaphragm 186, and the parts of the ampoule 180assume the positions illustrated in FIG. 16.

To ensure an intramuscular type injection, the needle 184 must passthrough the skin and the surface layers of fat and enter the muscleprior to medicament flow through the needle. Therefore, the chamber 190is designed so that its volume is greater than the total volume ofmedicament to be contained therein. Thus, as is illustrated in FIG. 16,there is a space Sp between the liquid level and the plunger 182 whenthe diaphragms 183 and 186 are drawn together. Prior to effecting aninjection, the plunger 182 is further depressed until the plunger 182contacts the surface of the liquid in the chamber 190. This operationprojects the needle 184 a predetermined distance beyond the diaphragm186, which distance substantially corresponds to the normal maximumdepth of the muscle beneath the skin of the patient, and air or gas inthe chamber 190 is substantially fully expelled in the process aspreviously described with reference to FIGS. 5-8.

An injection may then be performed by removing the needle guard 188 andmanually applying the ampoule 180 against the skin of the patient sothat the needle 184 penetrates the skin and enters the muscle. Afterthis operation, the plunger 182 is completely depressed to inject themedicament into the muscle. Desirably, however, the injection isperformed by an applicator which may generally correspond to theapplicator.

Referring now to FIGS. 19 and 20, the ampoule 110 is assembled andfilled by first attaching the needle 118 to the plunger 116 aspreviously described with reference to FIGS. 2-4 and then inserting theplunger in one end of the cylinder 11], as shown in FIG. 19. With theopen mouth of the cylinder 111 in an upright position, the cylinder 111is at least partially filled with the powdered medicament 123 and issubjected to a vacuum during or at the conclusion of the introduction ofpowdered medicament. While subjected to the vacuum, the first diaphragmis applied to the mouth of the cylinder. Thereafter, the second cylinder112 is applied to the diaphragm 115, as illustrated in FIG. 20. Thesecond cylinder 112 is then filled with a liquid medicament, and theremaining components are assembled to provide the ampoule shown in FIGS.9 to 13.

The invention is not restricted to the slavish imitation of each andevery detail set forth above. Obviously, hypodermic devices may beprovided; which change, eliminate or add certain specific detailswithout departing from the scopeof the invention.

What is claimed is:

1. A method of performing an intramuscular injection comprising thesteps of:

A. providing a hypodermic ampoule comprising:

a. a cylinder,

b. a diaphragm closing and sealing one end of said cylinder and having acentral, puncturable portion,

0. a slidable plunger in the opposite end of said cylinder and spacedfrom said diaphragm to provide a chamber therebetween,

. a liquid medicament in said chamber,

e. a hollow needle disposed in said chamber and extending axiallythereof from said plunger to said diaphragm for piercing the diaphragmupon inward movement of the plunger, said needle having an opening fromsaid chamber into the needle at one end adjacent said plunger and anopposite, pointed, discharge end adjacent said diaphragm,

the volume of medicament in said chamber being substantially less thanthe initial volume of said chamber so that, when the axis of saidcylinder .is vertically disposed with its plunger end uppermost, saidplunger is initially sufficiently spaced from the medicament to permitit to be moved inwardly for moving the pointed end of the needle throughand beyond said diaphragm before the plunger contacts the medicament toexpress it through the needle;

B. preprojecting said needle by moving said plunger inwardly until itsubstantially contacts the medica ment, so that the pointed end. of theneedle pierces the diaphragm and so that a portion of the needle extendsbeyond said diaphragm; after preprojecting said needle, projecting saidextended needle portion through the skin of a patient so that thepointed end of the needle enters a muscle of the patient and;

C. further moving the plunger inwardly to inject medicament into saidmuscle.

1. A method of performing an intramuscular injection comprising thesteps of: A. providing a hypodermic ampoule comprising: a. a cylinder,b. a diaphragm closing and sealing one end of saId cylinder and having acentral, puncturable portion, c. a slidable plunger in the opposite endof said cylinder and spaced from said diaphragm to provide a chambertherebetween, d. a liquid medicament in said chamber, e. a hollow needledisposed in said chamber and extending axially thereof from said plungerto said diaphragm for piercing the diaphragm upon inward movement of theplunger, said needle having an opening from said chamber into the needleat one end adjacent said plunger and an opposite, pointed, discharge endadjacent said diaphragm, the volume of medicament in said chamber beingsubstantially less than the initial volume of said chamber so that, whenthe axis of said cylinder is vertically disposed with its plunger enduppermost, said plunger is initially sufficiently spaced from themedicament to permit it to be moved inwardly for moving the pointed endof the needle through and beyond said diaphragm before the plungercontacts the medicament to express it through the needle; B.preprojecting said needle by moving said plunger inwardly until itsubstantially contacts the medicament, so that the pointed end of theneedle pierces the diaphragm and so that a portion of the needle extendsbeyond said diaphragm; after preprojecting said needle, projecting saidextended needle portion through the skin of a patient so that thepointed end of the needle enters a muscle of the patient and; C. furthermoving the plunger inwardly to inject medicament into said muscle.